Responses To Yohimbine in Social Phobia

Abstract

A recent report by Tancer et al.(1993) observed that the growth hormone response to clonidine was blunted in social phobics relative to controls. The current project aimed to further evaluate NE functioning in social phobia (SP) patients by administration of an IV challenge dose of the alpha 2 adrenoreceptor antagonist, yohimbine. METHOD: Six medication-free patients with a principal DSM-III-R diagnosis of SP (4 males, 2 females), without a history of spontaneous panic attacks, participated in the protocol. Two of the six patients met criteria for the specific SP subtype. Patients received 2 challenge tests approximately 1 week apart. On one test day yohimbine 0.4 mg/kg IV was infused, while a saline placebo was administered on the second day. Tests were administered in a double-blind, balanced manner. Within challenge measures included the Social Anxiety Questionnaire (SAQ) (0-10 intensity scale), a clinician-rated instrument designed to be sensitive to changes in social anxiety symptoms and a visual analog anxiety scale (VAS) rated by patients (0-100 mm scale). In addition blood samples were drawn serially for analysis of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). RESULTS: The mean peak change from baseline score in SAQ intensity was = 2.8±1.6 during the yohimbine test and = 0±0 (paired t-test t=3.8, df=4, p<0.05) during the placebo. The mean peak change±SD from baseline score in VAS anxiety was =10±12 mm for yohimbine vs 3±11 mm for placebo (t=0.89, df=5, p=0.42). Peak behavioral effects were noted 15 minutes post-yohimbine infusion. Peak change scores for plasma MHPG were = 2.1±0.9 ng/ml following yohimbine vs 0.7±0.9 ng/ml following placebo (t=2.7, df=4, p<0.06). CONCLUSIONS: These data suggest that yohimbine exacerbates social anxiety intensity and that this behavioral change is paralleled by concomitant increases in plasma levels of the NE metabolite, MHPG. Presynaptic dysfunction in the brain NE system may play a role in the pathophysiology of social phobia. Further studies are indicated to delineate the nature of this abnormality and its implications for treatment.